Method and apparatus for resonant wave mixing in closed containers

Abstract

A method and apparatus is provided for non-invasively mixing ingredients in closed containers. Mixing is performed by inducing waves in the liquid to be mixed. This is achieved by rocking the container in precise phase so as to produce resonance. With the waves moving back and forth in resonance, it is possible to mix with very low energy requirements compared to prior art. Mixing ingredients with resonant waves in a closed container eliminates the need for an invasive mixer and has obvious advantages in minimizing contamination. This makes the device ideal for biological processing that typically require sterile operation.

Description

BACKGROUND OF THE INVENTION [0001] 1. Field of the Invention [0002] The present invention relates to mixing of ingredients in closed containers, which may be rigid or flexible, such as bags. Typical applications are pharmaceutical and biological manufacturing, and involve the dissolution of solids, reconstitution of biological media, and mixing of sterile suspensions. [0003] 2. Description of the Related Art [0004] In various industries, especially pharmaceuticals, many materials are stored in disposable plastic bottles and bags. These one-use containers are very cost effective because they do not require to be cleaned and sterilized prior to and after use. Such bags and bottles are used to store dry ingredients prior to reconstitution, such as components for buffers and liquids such as culture media; or solutions, such as intermediate products prior to further processing. [0005] The major limitation to the increased use of such containers is the inability to mix the ingredients con...

AI Technical Summary

Benefits of technology

[0024] (d) Provides complete isolation of ingredients in the bag from the environment during mixing, allowing the bag to be handled in a non-aseptic environment, making it useful for the production of sterile materials, or mixing of pathogens, viruses and other substances requiring a high degree of containment. This “closed” operation may be achieved by using a sealed bag, or by providing filtered vents that prevent to influx or venting of contaminants.

[0025] Further objects and advantages of my invention will become apparent from a consideration of the drawings and ensuing description.

Problems solved by technology

The major limitation to the increased use of such containers is the inability to mix the ingredients contained in the bag.

This is especially serious with large bags (capacities of 10 to 1000 liters) which cannot be shaken by hand.

This method has several drawbacks—1) the need for an expensive rigid mixing tank and mixer that must be cleaned before and after use; 2) the need for a second disposable container for the material after mixing; 3) difficulty in maintaining sterility during this operation; and 4) significant labor-intensive fluid transfers.

This method is of very limited effectiveness.

Firstly, materials tend to sediment in the corners of the bag where the dip tube cannot reach, so that they are never dispersed.

Secondly, for effective mixing a high pump-around flow rate is required.

This causes the wall of the bag to collapse, choking off the flow in the pump-around loop and decreasing the mixing efficiency.

However, a simple calculation of power input and fluid properties will show that this method cannot impart sufficient energy to mix a bag larger than say 5 liters in volume within a reasonable period of time.

Thus, it is useless for the majority of mixing applications that involve mixing 10 to 1000 liters of liquid in a bag.

They are restricted to small volumes (less than 4 liters) since the cost of mechanisms necessary to handle the inertia and momentum of greater masses is prohibitive.

The mixing conditions cited in these shaker patents are far too harsh for biological fluids.

It is also doubtful that a flexible bag could be made that would withstand this high speed shaking.

Thus, such shaking devices are of little use in developing a method for mixing large volumes (5 to 1000 liters) of biological fluids.

While these methods are quite efficient, they are not useful for general purpose use nor can they be scaled up to the large volumes necessary.

These methods are not usable with standard storage bags, which consist of a single chamber of “pillow” or “cube” construction with single inlet and outlet ports.

The reason for this poor mixing efficiency is the lack of gas-filled headspace in the mixing bag of Katz.

These techniques are not suitable for low viscosity (1 to 20 cP) fluids typical of biological applications.

These conditions result in an expensive bag necessary to withstand the high stresses resulting from the high rocking rate and angle.

The energy consumption to achieve mixing is also quite large, making this method not very desirable for mixing applications, especially for large volumes.

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